rs111464924

Variant names:

• chrX-50042407-C-G
• rs111464924
• NM_001127898.4:c.108C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-50042407-C-G
• chrX-50042407-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001127898.4(CLCN5):​c.108C>G​(p.Thr36Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T36T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CLCN5 NM_001127898.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

Genes affected

CLCN5 (HGNC:2023): (chloride voltage-gated channel 5) This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.294 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCN5	NM_001127898.4	c.108C>G	p.Thr36Thr	synonymous_variant	Exon 4 of 15	ENST00000376091.8	NP_001121370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCN5	ENST00000376091.8	c.108C>G	p.Thr36Thr	synonymous_variant	Exon 4 of 15	2	NM_001127898.4	ENSP00000365259.3
CLCN5	ENST00000376088.7	c.108C>G	p.Thr36Thr	synonymous_variant	Exon 4 of 15	2		ENSP00000365256.3
CLCN5	ENST00000482218.2	c.108C>G	p.Thr36Thr	synonymous_variant	Exon 3 of 3	3		ENSP00000476732.1
CLCN5	ENST00000643129.1	n.69C>G		non_coding_transcript_exon_variant	Exon 1 of 14			ENSP00000496056.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.5
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs111464924; hg19: chrX-49807016;